Case Report High Fever As an Initial Symptom of Primary Gastric Inflammatory Myofibroblastic Tumor in an Adult Woman

Int J Clin Exp Med 2014;7(5):1468-1473 www.ijcem.com /ISSN:1940-5901/IJCEM0000684

Case Report High fever as an initial symptom of primary gastric inflammatory myofibroblastic tumor in an adult woman

Jiang-Feng Qiu, Yi-Jiu Shi, Lei Fang, Hui-Fang Wang, Mou-Cheng Zhang

Department of Gastrointestinal Surgery, Ningbo First Hospital, Ningbo, 315010, China Received March 29, 2014; Accepted May 9, 2014; Epub May 15, 2014; Published May 30, 2014

Abstract: Inflammatory myofibroblastic tumor, also known as inflammatory pseudotumor, plasma cell granuloma or inflammatory myofibroblastoma, is characterized histopathologically by myofibroblastic spindle cells with inflammatory cell infiltrates composed of plasma cells, lymphocytes and eosinophils. Inflammatory myofibroblastic tumor is typically seen in children or young adults and is most commonly localized to the lungs, but it can occur anywhere in the body. To date, however, only a few cases involving the stomach have been reported. Herein, we present a case of gastric inflammatory myofibroblastic tumor in an adult woman with an initial symptom of high fever.

Keywords: Inflammatory myofibroblastic tumor, stomach, inflammatory pseudotumor, high fever, surgery

Introduction tenderness. Routine blood tests revealed mi- crocytic hypochromic anemia with a hemoglo- Inflammatory myofibroblastic tumor (IMT) is an bin level of 10.8 g/dl and a hematocrit of 34.3%. uncommon mesenchymal neoplasm occurring Repeated blood cultures came up negative for mainly in children and young adults. IMT was the presence of bacteria or fungus. Radio- first described in the lung, but has since been logically, chest X-rays were normal, but con- observed in a wide variety of extrapulmonary trast-enhanced abdominal computed tomogra- sites such as the liver, urinary bladder, mesen- phy (CT) showed a 3.0 × 3.0 cm low-density tery, retroperitoneum, omentum and central mass located on the lesser curvature of the nervous system [1]. IMT is rarely seen in the stomach, near the angular incisure, and with stomach, especially in adults [2]. Here we several enlarged lymph nodes around it (Figure report a case of primary gastric IMT in an adult 1). Flexible upper digestive endoscopy identi- woman with high fever as the initial symptom. fied a small, superficial mucosal lesion in the The clinical and histopathological features of gastric antrum, and endoscopic ultrasound this rare lesion are described with a review of (EUS) showed a round hypoechoic mass, 3.0 × the literature. 3.0 cm in diameter, originating from the muscularis propria layer (Figure 2). Endoscopic biopsy Case presentation revealed inflamed gastric mucosa. Upon admis- A 61-year-old female was admitted to the emer- sion, the patient was initially administered intra- gency department suffering from a high fever of venous piperacillin and tazobactam for 3 days, 39.8°C. She had been experiencing intermit- followed by 3 days of intravenous meropenem, tent epigastric pain and abdominal distention but her temperature continued to fluctuate over a period of 5 days before fever developed, between 39°C and 39.8°C. The patient’s tem- but had no other presenting symptoms such as perature finally returned to normal after being cough, nausea, vomiting, hematochezia, reflux, treated with dexamethasone and indome- asthma or shivering. In addition, she had no thacin. history of alteration in bowel habits. Her past medical history was unremarkable, with the Based on the findings described above, a diag- exception of hypertension for the past 10 years. nosis of gastric sarcoma was suspected, and surgical excision was recommended due to the Clinical examination did not reveal any palpable presence of a gastric mass with unclear tumor abdominal mass and there were no signs of histology. The patient therefore underwent Gastric inflammatory myofibroblastic tumor in a woman

Figure 1. Abdomen CT scan. CT scan shows a 3.0 × 3.0 cm low-density mass, marked with the arrow, located on the lesser curvature near the angular incision.

Figure 2. Flexible upper GI endoscopy. A small, superficial mucosal lesion marked with the arrow in the gastric antrum is demonstrated (A). EUS shows a round hypoechoic mass, 3.0 × 3.0 cm in diameter, originating from the muscularis propria layer (B).

CD35, IGg4 and anaplastic lymphoma kinase exploratory laparotomy 10 days after admis- (ALK) (Figure 3). The immunological and mor- sion, during which the tumor’s location in the phological findings were found to be consistent lesser curvature near the angular incisure was with the diagnosis of IMT in the present case. confirmed, where it was found to have infiltrat- The postoperative course was uneventful, and ed the entire thickness of the gastric wall. the patient appears to be doing well over 3 Several enlarged lymph nodes were observed months of follow-up. near the tumor, but no signs of adjacent organ invasion or metastasis were detected. A radical Discussion surgical procedure was performed including a distal gastrectomy with D2 lymph node dissec- IMT has been characterized as a histologically tion and Billroth I reconstruction. Histopa- distinctive lesion with unpredictable behavior. thological examination of the tumor revealed While there was previous debate as to whether spindle cells with inflammatory infiltrate of neu- IMT is a tumor or inflammation, it is now recog- trophils, eosinophils, lymphocytes and plasma nized as a neoplasm of intermediate biological cells. Immunohistochemical analysis showed potential, with frequent recurrences and only that the tumor cells were positive for vimentin occasional metastasis [3]. The etiopathogene- and smooth muscle actin (SMA), but negative sis of IMT remains unclear. Various mecha- for cytokeratin (CK), CD117, CD21, CD23, nisms of tumor development have been postu-

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Figure 3. Microscopy of gastric IMT. Image shows spindle cells with inflammatory cell infiltration (A). Immunohisto- chemistry reveals the presence of vimentin (B) and smooth muscle actin (SMA) (C); whereas negative for ALK (D), CD117 (E), CK (F), CD21 (G), CD23 (H), CD35 (I) and IGg4 (J) (HE staining ×10). lated, including exaggerated inflammatory tumor (GIST), leiomyoma and follicular dendritic response to infections and rearrangement of cell sarcoma (FDCS) that must be distinguished the ALK gene [4, 5]. As stated previously, it from IMT. Usually, IFP, GIST and smooth muscle occurs mainly in children and young adults, and tumors do not display the systemic symptoms the lungs are the most commonly affected site. as seen in IMT patients. The definitive diagno- Primary gastric IMTs in adults are very rare. To sis should be verified by a histopathological date, only 16 adult patients with gastric IMT study. IFP is a benign tumor-like lesion which have been reported based on the available lit- rarely invades the muscularis. The tumor cells erature, with a male to female ratio of 1 to 4 [6, in IFP also present an onion skin-like pattern 7]. Clinical and pathological findings from a around blood vessels and glands which is review of 16 cases of gastric IMT in adults that absent in IMT. Immunohistochemically, IFP has been reported are summarized in Table 1. mostly presents positive for CD34 but negative for SMA [17]. In the present case, IFP was Gastric IMT typically present with abdominal therefore ruled out by the transmural location, pain, hematemesis, melena and a palpable lack of onion skinning on histology and immu- abdominal mass. Weight loss, fever and hypo- nopositivity for SMA. GIST microscopically chromic anemia may also be associated with shows only scattered inflammatory cells, and gastric IMT. To our knowledge, however, the immunohistochemically nearly always presents present case is the first report of primary gas- positive for CD117 and DOG1 which was oppo- tric IMT in adults with high fever of almost 40°C site for IMT [18]. Although leiomyoma can show as the initial and main symptom. myxoid change and occasional eosinophilic infiltrates with immunohistochemically positive Radiologically, there is no specific feature to the for SMA, leiomyomas do not demonstrate IMT [16]. Pre-surgical EUS and CT may help to marked lymphoplasmacytic infiltrates and determine the extragastric invasion. Due to the sparsely arranged spindle cells, moreover, leio- tumor’s submucosal location, endoscopic biop- myomas often show numerous scattered sies frequently reveal only normal gastric CD117 positive mast cells, which helped in dif- mucosa. Surgical exploration with complete ferentiating it from IMT [7]. Follicular dendritic resection is therefore the most efficient treat- cell sarcoma is a malignant neoplasm derived ment method and can meanwhile obtain an from follicular dendritic cell that possess and accurate histological diagnosis. The histologi- present antigens to B cells in the follicular cen- cal appearance of gastric IMT is characterized ters of lymphoid organs. They often occur in by proliferation of spindle-shaped myofibro- lymph nodes, although they can also arise at blastic cells and a lymphoplasmacytic infiltrate extranodal sites. Histologically, the characteris- distributed among the tumor cells. Immu- tics of FDCS are whorl, storiform and fascicular nohistologically, IMT cells are usually positive arrangements of oval to spindle tumor cells for vimentin, SMA, desmin, but negative for with indistinct cell borders. Immunohisto- CD117 and S-100. There are a few tumors or chemically, the most sensitive and specific lesions in the stomach such as inflammatory markers for FDCS are positive for CD21, CD23 fibroid polyp (IFP), gastrointestinal stromal and CD35 but negative for CK which may be

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Table 1. Review of patient characteristics of previously reported gastric IMT Age/ Tumor ALK Author Presenting symptoms Tumor location Treatment Follow-up sex size status 1 Kojimahara et al. 1993 [8] 19/F Vomiting, Weight loss C to LC 9 cm TG NA Asymptomatic at 2.5 years 2 Al-Taie et al. 2002 [9] 45/F Abdominal pain Body 6 cm PG NA Not available 3 Kim et al. 2004 [10] 26/M Palpable lump, anemia C to body 8 cm TG NA 7 cm mass in rectovesical pouch at 5 weeks 4 Leon et al. 2006 [2] 50/F Vomiting, Weight loss PW 7 cm SG NA Asymptomatic at 2 years 5 Park et al. 2008 [11] 55/F Abdominal pain GC 8.5 cm Gastric wedge resection Negative No recurrence 6 Shah et al. 2008 [4] 80/F Epigastric discomfort, anemia Prepyloric region 1.5 cm Excision NA Asymptomatic 7 Albayrak et al. 2010 [12] 56/F Hematemesis, melena, vomiting C 11 cm PG Negative Asymptomatic at 8 months s 8 Shi et al. 2010 [13] 36/M Abdominal pain and mass Antrum, LC 4.5 cm PG Positive NED at 5 years 9 Shi et al. 2010 [13] 42/M Abdominal pain and mass, upper GI hemorrhage Upper Body, GC 8 cm PG Positive NED at 2 years 10 Shi et al. 2010 [13] 40/M Abdominal mass Upper Body, AW 6.3 cm PG Positive NED at 3.3 years 11 Shi et al. 2010 [13] 45/M Abdominal mass and pain Angle 5.5 cm PG Positive NED at 2.6 years 12 Shi et al. 2010 [13] 40/F Abdominal pain and mass Lower Body, PW 5.8 cm PG Positive NED at 4 years 13 Jain et al. 2012 [7] 35/F Abdominal pain, vomiting, anemia GC 11 cm Wide excision Negative Asymptomatic at 7 months 14 Ribeiro et al. 2012 [14] 37/F Epigastric pain, Weight loss Lower body 9.0 cm SG Positive Not available 15 Bjelovic et al. 2013 [6] 43/F Abdominal pain, nausea Distal stomach 6 cm DG Positive 2 years 16 Arslan et al. 2013 [15] 65/F Dyspepsia, Intermittent Epigastric pain antrum 11 cm Gastric wedge resection Positive NED at 3 months 17 Present case 61/F High fever LC 3.0 cm DG Negative NED at 3 months Abbreviations: C, cardia; F, female; M, male; LC, lesser curvature of the stomach; GC, greater curvature of the stomach; AW, anterior wall of the stomach; PW, posterior wall of the stomach; PG, partial gastrectomy; DG, distal gastrectomy; SG, subtotal gastrectomy; TG, total gastrectomy; NED, no evidence of disease; NA, not available.

1471 Int J Clin Exp Med 2014;7(5):1468-1473 Gastric inflammatory myofibroblastic tumor in a woman used to discriminate FDCS from IMT [19, 20]. Hospital, Ningbo, 315010, PR China. Tel: 0086- IgG4-related inflammatory pseudotumor (IPT) 0574-87089859; Fax: 0086-0574-87304070; and IMT share the similar morphological fea- E-mail: [email protected] tures as proliferation of spindle cells along with fibrosis and an inflammatory infiltrate compris- References ing of lymphocytes and plasma cells. However, [1] Coffin CM, Watterson J, Priest JR, Dehner LP. the spindle cell proliferation is more obvious in Extrapulmonary inflammatory myofibroblastic IMT whereas lymphoplasmacytic infiltrate is tumor (inflammatory pseudotumor). A clinico- more notable in IPT. Immunohistochemically, pathologic and immunohistochemical study of IPT often shows marked positive for IgG4 but 84 cases. Am J Surg Patho 1995; 19: 859- negative for ALK. Although the present case 872. showed immunonegative for ALK, the marked [2] Leon CJ, Castillo J, Mebold J, Cortez L, Felmer proliferation of spindle cells and immunoposi- R. Inflammatory myofibroblastic tumor of the tive for vimentin and SMA but immunonegative stomach: an unusual complication after gas- for IgG4 are helped in differentiating these mor- trectomy. Gastrointest Endos 2006; 63: 347- 349. phologically similar but biologically different [3] Coffin CM, Hornick JL, Fletcher CD. Inflamma- lesions [21, 22]. tory myofibroblastic tumor: comparison of clini- Recently, ALK reactivity was found important in copathologic, histologic, and immunohistochemical features including ALK expression in the diagnosis of IMT and associated with local atypical and aggressive cases. Am J Surg recurrence thus suggesting that ALK reactivity Pathol 2007; 31: 509-520. may be a favorable prognostic indicator in IMT [4] Shah SM, Sussman D, Jorda M, Ribeiro A. EUS [3]. Approximately 60% of IMTs contain ALK with EMR of an inflammatory myofibroblastic proteins which can be detected by immunohis- tumor of the stomach. Gastrointest Endosc tochemistry and form a specific marker if posi- 2008; 67: 561-563. tive [5]. ALK-negative tumors are more seen in [5] Cook JR, Dehner LP, Collins MH, Ma Z, Morris older patients and likely to present atypical his- SW, Coffin CM, Hill DA. Anaplastic lymphoma tological features which was considered to be kinase(ALK) expression in the inflammatory associated with metastases [3, 7]. However, myofibroblastic tumor: a comparative immuno- other study did not confirm such an association histochemical study. Am J Surg Pathol 2001; [23]. Of the 17 cases of adult gastric IMT, ALK 25: 1364-1371. [6] Bjelovic M, Micev M, Spica B, Babic T, Gunjic D, immunohistochemistry was performed in 12 Djuric A, Pesko P. Primary inflammatory myofi- cases, and 4 cases (including our case) were broblastic tumor of the stomach in an adult negative for ALK. The status of ALK expression woman: a case report and review of the litera- in all of 17 cases of gastric IMT in adult was ture. World J Surg Onco 2013; 4: 11-35. seen in Table 1. [7] Jain A, Kasana S, Ramrakhiani D, Sharma M. Inflammatory myofibroblastic tumor of the The rate of recurrence for gastric IMTs is esti- stomach in an adult female report of a rare mated to somewhere between 15% and 37% case and review of the literature. Turk J Gastro- [24]. Factors that affect recurrence include entero 2012; 23: 399-405. tumor size, incomplete resection, presence of [8] Kojimahara K, Mukai M, Yamazaki K, Yamada multinodular masses and age. The first-line T, Katayama T, Nakada K, Uematsu S, Umezo- treatment for IMT is surgical resection. Some no A, Hosoda Y. Inflammatory pseudotumor of patients may also respond to treatment with the stomach: report of a highly infiltrative case dexamethasone and indomethacin. with electron microscopic and immunohistochemical studies. Acta Pathol Jpn 1993; 43: Acknowledgements 65-70. [9] Al-Taie OH, Mork H, Jenett M, Klein D, Müller We would like to thank Dr. Xiu-Chong Yu for her JG, Scheurlen M. Fast-growing gastric inflamm- help with the data collection. atory pseudotumor: a rare manifestation of Disclosure of conflict of interest peptic ulcer disease. Endoscopy 2002; 34: 239. None. [10] Kim KA, Park CM, Lee JH, Cha SH, Park SW, Hong SJ, Seol HY, Cha IH, Mok YJ, Kim YS. In- Address correspondence to: Dr. Jiang-Feng Qiu, De- flammatory myofibroblastic tumor of the stom- partment of Gastrointestinal Surgery, Ningbo First ach with peritoneal dissemination in a young

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